APETx2

APETx2, a peptide toxin effector of ASIC3, has been purified from an extract of the sea anemone Anthopleura elegantissima. APETx2 is a 42-amino-acid peptide cross-linked by three disulfide bridges. Its three-dimensional structure, as determined by conventional two-dimensional 1 H-NMR, consists of a compact disulfidebonded core composed of a four-stranded b-sheet. It belongs to the disulfide-rich all-b structural family encompassing peptide toxins commonly found in animal venoms.  >> Read More

The structural characteristics of APETx2 are compared with that of PcTx1, another effector of ASIC channels but specific to the ASIC1a subtype and to APETx1, a toxin structurally related to APETx2, which targets the HERG potassium channel.

Solution structure of APETx2, a specific peptide inhibitor of ASIC3 proton-gated channels

ASICs appear to be key mediators of inflammatory pain. ASIC antagonists and antisense oligonucleotides reduced both thermal and mechanical hyperalgesia in a rat model of inflammatory pain, highlighting the utility of selective pharmacological agents for studying ASIC channel function. Unfortunately, only two selective ASIC inhibitors have been discovered. The tarantula toxin PcTx1 is a specific blocker of homomeric ASIC1a channels, whereas the sea anemone peptide APETx2 blocks homomeric ASIC3 and ASIC3-containing heteromeric channels. PcTx1 is potently analgesic in mouse models of inflammatory and neuropathic pain, while APETx2 abolishes acid-induced pain in rats. Thus, APETx2 is an invaluable tool for study of ASIC3 channels.

Chemical synthesis and folding of APETx2, a potent and selective inhibitor of acid sensing ion channel 3